Our goals are to determine the pathways taken by water and solutes including gases across the pulmonary endothelial and epithelial boundaries and interstitial tissues and to characterize the factors and mechanisms of passage that are involved in the distribution of water and solutes among the several compartments accessible: blood, cells, interstitium, gas phase and boundary layers. In addition we seek the means of determining in vivo simply, rapidly and accurately, pulmonary blood flow, extra-vascular lung water, the vascular exchange volume (equivalent to a functional rather than anatomical capillary volume), solute extractions and permeability surface area products from which permeability coefficients can be calculated. Studies of filtration rates and of the significance of calculated filtration coefficients will also be carried out. The clinical implications are: insights into blood:gas exchanges in the lungs, the delivery of oxygen and the removal of carbon dioxide; measurement of the extent of pulmonary edema at the bedside and the assessment of small solute permeability coefficients to differentiate between "cardiac" or hemodynamic and permeability (e.g. adult respiratory distress syndrome) types of edema; an understanding of the pathways available to water and solutes for net passage and exchanges and their modifiability. The systems studied include isolated blood and lung cells, isolated and perfused lungs, organs in vivo. The methodologies include: linear diffusion for individual cell permeabilities and cell size for reflection and osmotic filtration coefficients; indicator dilution techniques for the measurement of functional parameters in isolated perfused lungs and in vivo; standard weight responses for measurement of whole organ filtration and osmotic coefficients; morphometric techniques for the measurement of structural features of vessels and interstitium and distributions of red cells and plasma in the lungs. In addition we are developing methodologies for the use of stable isotopes and non-radioactive markers rather than radioactive materials for studies with potential clinical use. Finally, we seek to develop techniques which will simplify the laboratory work and expedite completion of our studies through the use of on-line measurement procedures.